Trial Information

Allogeneic Bone Marrow Transplantation Using Less Intensive Therapy

OBJECTIVES:

- Determine if a nonmyeloablative regimen comprising cyclophosphamide, fludarabine, and radiotherapy followed by cyclosporine and mycophenolate mofetil provides a prompt and durable donor engraftment in patients with hematologic malignancies or kidney cancer who are undergoing allogeneic stem cell transplantation.

- Determine the safety of this nonmyeloablative transplantation regimen in these patients.

- Determine the risk of graft-versus-host-disease in patients treated with this regimen.

- Determine the antineoplastic potency of nonmyeloablative stem cell transplantation in patients treated with this regimen.

- Preparative regimen*: Patients receive cyclophosphamide intravenously (IV) over 2 hours on day -6 and fludarabine IV over 1 hour on days -6 to -2. Patients undergo total body irradiation on day -1. Some patients also receive anti-thymocyte globulin (ATG)** IV every 12 hours on days -6 to -4. Patients who receive ATG* include the following:

- Related donor recipients who have not received combination chemotherapy within the past 6 months

- Unrelated donor recipients who have not received combination chemotherapy within the past 3 months

- Graft-versus-host-disease prophylaxis: Patients receive cyclosporine IV over 2 hours beginning on day -3 and continuing until at least day 100. Patients also receive mycophenolate mofetil IV or orally twice daily on days -3 to 30.

- Acute myelogenous leukemia— high risk CR1 (as evidenced by preceding myelodysplastic syndrome [MDS], high risk cytogenetics such as those associated with MDS or complex karyotype, or > 2 cycles to obtain CR); second or greater complete remission (CR). Must be in remission by morphology. Patients in morphologic relapse/ persistent disease defined as > 5% blasts in normocellular bone marrow OR any % blasts if blasts have unique morphologic markers (eg auer rods) or associated cytogenetic markers that allows morphologic relapse to be distinguished are not eligible for arms 2 or 3.

Note cytogenetic evidence of disease alone without morphologic relapse is acceptable. Also a small percentage of blasts that is equivocal between marrow regeneration vs early relapse is acceptable provided there are no associated cytogenetic markers consistent with relapse.

- Acute lymphocytic leukemia-- high risk CR1 as evidenced by high risk cytogenetics (eg t(9;22) or complex cytogenetic abnormalities) or > 1 cycle to obtain CR; second or greater CR. Must be in remission by morphology. Patients in morphologic relapse/ persistent disease defined as > 5% blasts in normocellular bone marrow OR any % blasts if blasts have unique morphologic markers or associated cytogenetic markers that allows morphologic relapse to be distinguished are not eligible for arms 2 or 3. Note cytogenetic relapse or persistent disease without morphologic relapse is acceptable. Also a small percentage of blasts that is equivocal between marrow regeneration vs early relapse is acceptable provided there are no associated cytogenetic markers consistent with relapse.

- Myelodysplastic syndrome of all subtypes including refractory anemia (RA) or all IPSS categories if severe pancytopenia, transfusion requirements not responsive to therapy, or high risk cytogenetics. Blasts must be less than 5%. If >5% requires therapy (induction or Hypomethylating agents) pre-transplant to decrease disease burden.

- Renal cell cancer,

- Chronic myeloproliferative disorder, i.e. myelofibrosis

- Disease Criteria (High risk patients on Arm 7)

- Patients with refractory leukemia or MDS may be taken to transplant in aplasia after induction or re-induction chemotherapy or radiolabeled antibody. These high risk patients will be analyzed separately in Arm 7.

- If recent mold infection (e.g. aspergillus) must have minimum of 30 days of therapy and responsive disease and be cleared by Infectious Disease.

- Albumin > 2.5

Exclusion Criteria:

- Pregnancy or breast feeding

- Evidence of HIV infection or known HIV positive serology

- Active serious infection

- Congenital bone marrow failure syndrome

- Previous irradiation that precludes the safe administration of an additional dose of 200 cGy of total body irradiation (TBI)

- Chronic myelogenous leukemia (CML) in refractory blast crisis

- Intermediate or high grade NHL, mantle cell NHL, and Hodgkins disease that is progressive on salvage therapy. Stable disease is acceptable to move forward provided it is non-bulky.

- Multiple Myeloma progressive on salvage chemotherapy.

DONOR ELIGIBILITY

- Related will undergo apheresis - if donor is unable to undergo apheresis, a bone marrow harvest is acceptable; unrelated volunteer donors must be able to undergo bone marrow harvest or apheresis.

- All donors must be able to give informed consent.

- Donors weighing less than 40 kg (children) will need evaluation by a pediatrician for suitability of the apheresis procedure. Informed consent must be obtained from parent or guardian as applicable for minors.

Type of Study:

Study Design:

Outcome Measure:

Neutrophil and Donor Cell Engraftment

Outcome Description:

Successful sustained engraftment is defined as primary neutrophil engraftment by day 42 and e90% donor cells at day 100, with or without DLI.
Engraftment based on absolute neutrophil count of donor origin > 0.5 x 10e9 /L for 3 days by day 42

Outcome Time Frame:

Day 42 and Day 100

Safety Issue:

No

Principal Investigator

Erica Warlick, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Masonic Cancer Center, University of Minnesota

Authority:

United States: Food and Drug Administration

Study ID:

2001LS058

NCT ID:

NCT00303719

Start Date:

March 2002

Completion Date:

January 2015

Related Keywords:

Kidney Cancer

Leukemia

Lymphoma

Multiple Myeloma

Plasma Cell Neoplasm

Myelodysplastic Syndromes

leukemia

lymphoma

myeloma

Neoplasms

Carcinoma, Renal Cell

Kidney Neoplasms

Leukemia

Lymphoma

Multiple Myeloma

Neoplasms, Plasma Cell

Plasmacytoma

Myelodysplastic Syndromes

Preleukemia

Name

Location

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